Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 83
Filter
1.
Aesthet Surg J ; 43(9): 986-993, 2023 08 17.
Article in English | MEDLINE | ID: mdl-37265092

ABSTRACT

BACKGROUND: Patients seeking cosmetic abdominoplasty often have umbilical hernias. Optimal management and safety of concomitant umbilical hernia repair with abdominoplasty is not well described. OBJECTIVES: The goal of this study was to compare complication rates following abdominoplasty with or without umbilical hernia repair. METHODS: A retrospective propensity score matched cohort study of patients who underwent an abdominoplasty at Massachusetts General Hospital was performed. Direct umbilical hernia repair was performed by making a fascial slit inferior or superior to the umbilical stalk. The fascial edges were approximated with up to three 0-Ethibond sutures (Ethicon, Raritan, NJ) from the preperitoneal or peritoneal space. Propensity score matching was used to adjust for confounding variables. RESULTS: The authors identified 231 patients with a mean [standard deviation] age of 46.7 [9.7] years and a mean BMI of 25.9 [4.4] kg/m2. Nine (3.9%) had diabetes, 8 (3.5%) were active smokers, and the median number of previous pregnancies was 2. In total, 223 (96%) had a traditional abdominoplasty, whereas 8 (3.5%) underwent a fleur-de-lys approach. Liposuction was performed on 90%, and 45.4% underwent simultaneous breast or body contouring surgery. The overall complication rate was 6.9%. Propensity scores matched 61 pairs in each group (n = 122) with closely aligned covariates. There was no significant difference in total complication rates between abdominoplasty alone vs abdominoplasty with hernia repair. There were no cases of skin necrosis or umbilical necrosis in either group. CONCLUSIONS: Performing umbilical hernia repair with abdominoplasty is safe when utilizing the technique reported in this series.


Subject(s)
Abdominoplasty , Hernia, Umbilical , Humans , Child , Hernia, Umbilical/surgery , Propensity Score , Cohort Studies , Retrospective Studies , Abdominoplasty/adverse effects , Abdominoplasty/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Necrosis/surgery
2.
RSC Chem Biol ; 4(6): 422-430, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37292058

ABSTRACT

Diacylglycerol kinases (DGKs) are metabolic kinases involved in regulating cellular levels of diacylglycerol and phosphatidic lipid messengers. The development of selective inhibitors for individual DGKs would benefit from discovery of protein pockets available for inhibitor binding in cellular environments. Here we utilized a sulfonyl-triazole probe (TH211) bearing a DGK fragment ligand for covalent binding to tyrosine and lysine sites on DGKs in cells that map to predicted small molecule binding pockets in AlphaFold structures. We apply this chemoproteomics-AlphaFold approach to evaluate probe binding of DGK chimera proteins engineered to exchange regulatory C1 domains between DGK subtypes (DGKα and DGKζ). Specifically, we discovered loss of TH211 binding to a predicted pocket in the catalytic domain when C1 domains on DGKα were exchanged that correlated with impaired biochemical activity as measured by a DAG phosphorylation assay. Collectively, we provide a family-wide assessment of accessible sites for covalent targeting that combined with AlphaFold revealed predicted small molecule binding pockets for guiding future inhibitor development of the DGK superfamily.

3.
Sci Transl Med ; 15(683): eade6023, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36791210

ABSTRACT

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.


Subject(s)
Antibody Formation , COVID-19 , Humans , Aged , BNT162 Vaccine , SARS-CoV-2 , Immunoglobulin G , Antibodies, Viral
4.
Methods Mol Biol ; 2625: 365-370, 2023.
Article in English | MEDLINE | ID: mdl-36653658

ABSTRACT

Liposomes are spherical vesicles with a wide range of sizes from nano- to micrometer scale. For the past 7-8 decades, these vesicles have gained the interest of many scientists due to their physical, chemical, and mathematical properties and for their immense utility and potential as delivery vehicles for toxic and non-toxic excipients into biological tissues. Methods related to the selection of reagents for the creation of specific liposomes of certain properties are beyond the scope of this chapter, but here, I would outline a simplistic protocol to prepare and qualify a uniform batch of simple liposomes with basic cargo. This chapter will attempt to provide the reader with a starting point for this immensely potent tool.


Subject(s)
Liposomes , Sonication , Liposomes/chemistry , Sonication/methods
5.
Arch. cardiol. Méx ; 92(4): 541-544, Oct.-Dec. 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1429691

ABSTRACT

Abstract A 53-year-old man with an asymptomatic fistula from the Vieussens ring to the pulmonary artery presented with progressive respiratory distress. Coil embolization of this type of fistula has been described by femoral access. The advanced transradial "grandmother-mother-son" technique for high active support safely allows successful embolization of this type of coronary fistulae.


Resumen Un hombre de 53 años con una fístula asintomática del anillo de Vieussens a la arteria pulmonar comenzó con dificultad respiratoria progresiva. La embolización con coils de este tipo de fístulas ha sido descrita por acceso femoral. La técnica transradial avanzada "abuela-madre-hijo" para un alto soporte activo permite de manera segura la embolización exitosa de este tipo fístulas coronarias.

6.
Arch Cardiol Mex ; 92(4): 541-544, 2022.
Article in English | MEDLINE | ID: mdl-36413689

ABSTRACT

A 53-year-old man with an asymptomatic fistula from the Vieussens ring to the pulmonary artery presented with progressive respiratory distress. Coil embolization of this type of fistula has been described by femoral access. The advanced transradial "grandmother-mother-son" technique for high active support safely allows successful embolization of this type of coronary fistulae.


Un hombre de 53 años con una fístula asintomática del anillo de Vieussens a la arteria pulmonar comenzó con dificultad respiratoria progresiva. La embolización con coils de este tipo de fístulas ha sido descrita por acceso femoral. La técnica transradial avanzada "abuela-madre-hijo" para un alto soporte activo permite de manera segura la embolización exitosa de este tipo fístulas coronarias.


Subject(s)
Coronary Vessel Anomalies , Fistula , Grandparents , Male , Humans , Middle Aged , Pulmonary Artery , Coronary Angiography/methods , Mother-Child Relations
7.
Gut Microbes ; 14(1): 2096328, 2022.
Article in English | MEDLINE | ID: mdl-35816618

ABSTRACT

Obesity causes chronic inflammation and changes in gut microbiome. However, how this contributes to poor survival and therapy resistance in patients with pancreatic cancer remain undetermined. Our current study shows that high fat diet-fed obese pancreatic tumor bearing mice do not respond to standard of care therapy with gemcitabine and paclitaxel when compared to corresponding control diet-fed mice. C57BL6 mice were put on control and high fat diet for 1 month following with pancreatic tumors were implanted in both groups. Microbiome of lean (control) and obese (high fat diet fed) mice was analyzed. Fecal matter transplant from control mice to obese mice sensitized tumors to chemotherapy and demonstrated extensive cell death. Analysis of gut microbiome showed an enrichment of queuosine (Q) producing bacteria in obese mice and an enrichment of S-adenosyl methionine (SAM) producing bacteria in control diet-fed mice. Further, supplementation of obese animals with SAM sensitized pancreatic tumors to chemotherapy. Treatment of pancreatic cancer cells with Q increased PRDX1 involved in oxidative stress protection. In parallel, tumors in obese mice showed increase in CD133+ treatment refractory tumor populations compared to control animals. These observations indicated that microbial metabolite Q accumulation in high fat diet-fed mice protected tumors from chemotherapy induced oxidative stress by upregulating PRDX1. This protection could be reversed by treatment with SAM. We conclude that relative concentration of SAM and queuosine in fecal samples of pancreatic cancer patients can be developed as a potential biomarker and therapeutic target in chemotherapy refractory pancreatic cancer.


Subject(s)
Gastrointestinal Microbiome , Pancreatic Neoplasms , Animals , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome/physiology , Mice , Mice, Inbred C57BL , Nucleoside Q , Obesity/metabolism , Pancreatic Neoplasms/complications , Pancreatic Neoplasms
9.
Acta Paul. Enferm. (Online) ; 35: eAPE01326, 2022. tab
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-1393710

ABSTRACT

Resumo Objetivo Analisar as características associadas aos pais de crianças e adolescentes que ouviram falar sobre o Papillomavirus humano, bem como o conhecimento sobre a infecção e a intenção de vacinar seus filhos. Métodos Estudo transversal com abordagem quantitativa, realizado por meio de entrevista utilizando instrumento estruturado. Entrevistaram-se 376 pais de crianças e adolescentes que aguardavam atendimento pediátrico em unidades de saúde de Três Lagoas/MS. Os dados coletados (características sociodemográficas; características reprodutivas e sexuais; conhecimento sobre o Papillomavirus humano e intenção de vacinar o/a filho/a) foram analisados por meio de técnica de estatística descritiva, teste de associação Qui-quadrado ou exato de Fisher e Teste T Student. Resultados Dentre os entrevistados, 327 (87,0%) afirmaram ter ouvido falar sobre o Papillomavirus humano. Identificou-se associação entre os pais que nunca ouviram falar sobre a infecção e sexo masculino, idade entre 18 e 25 anos e ensino fundamental incompleto. Dentre os pais que ouviram falar sobre o Papilomavírus Humano, 152 (46,5%) afirmaram que é uma infecção sexualmente transmissível, 245 (74,9%) garantiram que a transmissão ocorre através da relação sexual desprotegida, 275 (75,5%) desconhecem seus sinais e sintomas, 218 (66,7%) afirmaram erroneamente que tal infecção tem cura e 283 (86,5%) sabem da existência da vacina. Dentre todos os entrevistados, 98,1% levariam seu(ua) filho(a) para vacinar contra o vírus. Conclusão Observaram-se lacunas no conhecimento dos pais de crianças e adolescentes sobre o Papillomavirus humano, mostrando a necessidade de educação em saúde e divulgação de ações de enfrentamento à infecção em meios de comunicação e redes sociais.


Resumen Objetivo Analizar las características asociadas a padres de niños y adolescentes que escucharon hablar sobre el virus del papiloma humano, así como el conocimiento sobre la infección y la intención de vacunar a sus hijos. Métodos Estudio transversal, con enfoque cuantitativo, realizado por medio de encuesta con instrumento estructurado. Se encuestaron 376 padres de niños y adolescentes que esperaban atención pediátrica en unidades de salud de Três Lagoas, estado de Mato Grosso do Sul. Los datos recopilados (características sociodemográficas, características reproductivas y sexuales, conocimiento sobre el virus del papiloma humano e intención de vacunar al hijo/a) se analizaron por medio de técnica de estadística descriptiva, prueba de asociación ji cuadrado o prueba exacta de Fisher y test-T Student. Resultados Entre los encuestados, 327 (87,0 %) afirmaron haber escuchado hablar sobre el virus del papiloma humano. Se identificó relación entre los padres que nunca escucharon hablar sobre la infección y el sexo masculino, edad entre 18 y 25 años y educación primaria incompleta. De los padres que escucharon hablar sobre el virus del papiloma humano, 152 (46,5 %) afirmaron que es una infección de transmisión sexual, 245 (74,9 %) aseguraron que la transmisión ocurre a través de las relaciones sexuales sin protección, 275 (75,5 %) desconocen sus signos y síntomas, 218 (66,7 %) afirmaron erróneamente que tal infección tiene cura, y 283 (86,5 %) saben de la existencia de la vacuna. Entre los encuestados, el 98,1 % llevaría a su hijo/a vacunarse contra el virus. Conclusión Se observaron vacíos de conocimiento en los padres de niños y adolescentes sobre el virus del papiloma humano, lo que muestra la necesidad de educación para la salud y difusión de acciones para enfrentar la infección en medios de comunicación y redes sociales.


Abstract Objective Analyze the characteristics associated with the parents of children and adolescents who have heard about the human papillomavirus, as well as the knowledge about the infection and the intention to vaccinate their children. Methods Cross-sectional study with quantitative approach, conducted through a structured interview. We interviewed 376 parents of children and adolescents who were awaiting pediatric care at health services in Três Lagoas/MS. The collected data (sociodemographic characteristics; reproductive and sexual characteristics; knowledge about human papillomavirus and intention to vaccinate the child) were analyzed using descriptive statistics, Fisher's exact test or the chi-square association test and Student's t-test. Results Among the respondents, 327 (87.0%) said they had heard about the human papillomavirus. An association was identified between parents who had never heard of the infection and male sex, age between 18 and 25 years and unfinished primary education. Among the parents who had heard about the human papillomavirus, 152 (46.5%) stated that it is a sexually transmitted infection, 245 (74.9%) assured that the transmission occurs through unprotected sexual intercourse, 275 (75.5%) are unaware of its signs and symptoms, 218 (66.7%) mistakenly stated that this infection is curable and 283 (86.5%) know of the existence of the vaccine. Among all respondents, 98.1% would take their child to get vaccinated against the virus. Conclusion Gaps were observed in the knowledge of the parents of children and adolescents about the human papillomavirus, showing the need for health education and dissemination of actions to cope with the infection in the media and social networks.


Subject(s)
Humans , Male , Female , Papillomaviridae , Parents/psychology , Attitude to Health/ethnology , Patient Acceptance of Health Care , Health Knowledge, Attitudes, Practice/ethnology , Knowledge , Papillomavirus Infections , Papillomavirus Vaccines , Child , Cross-Sectional Studies , Interviews as Topic , Adolescent
10.
Front Immunol ; 12: 748397, 2021.
Article in English | MEDLINE | ID: mdl-34737748

ABSTRACT

Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate the age associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 geriatric (age 19-24 years) and 4 young adult (age 3-4 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in peripheral blood mononuclear cells (PBMC) by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate, and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the gut microbiome in geriatric animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young adults. Highly abundant microbes in the geriatric animals showed a direct association with plasma biomarkers of inflammation and immune activation such as neopterin, CRP, TNF, IL-2, IL-6, IL-8 and IFN-γ. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of geriatric animals compared to the young adults. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile. Aging NHP can serve as a model for investigating the relationship of the gut microbiome to particular age-associated comorbidities and for strategies aimed at modulating the microbiome.


Subject(s)
Aging/immunology , Dysbiosis/microbiology , Gastrointestinal Microbiome , Inflammation/microbiology , Animals , Bacteria/metabolism , C-Reactive Protein/analysis , Cytokines/blood , Disease Models, Animal , Dysbiosis/immunology , Dysbiosis/metabolism , Feces/chemistry , Feces/microbiology , Female , Gastrointestinal Microbiome/physiology , Inflammation/immunology , Inflammation/metabolism , Macaca mulatta , Male , Symbiosis , Tandem Mass Spectrometry , Tumor Necrosis Factor-alpha/blood
11.
Acta Paul. Enferm. (Online) ; 34: eAPE00583, 2021. tab
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-1278063

ABSTRACT

Resumo Objetivo: Avaliar a qualidade de vida relacionada à saúde (QVRS) de pacientes oncológicos antes e três meses após o início do tratamento quimioterápico. Métodos: Tratou-se de um estudo de coorte prospectivo, exploratório. Foi utilizado um instrumento para caracterização sociodemográfi ca e clínica dos pacientes e outro para avaliação da QVRS denominado EORTC QLQ-C30, sendo este constituído por três escalas: funcionalidade, sintomas e saúde global. Participaram 79 indivíduos atendidos em um ambulatório para realização de quimioterapia. Testes estatísticos foram realizados para comparar o efeito do tratamento quimioterápico em relação à qualidade de vida. Resultados: O instrumento EORTC QLQ-C30 indicou adequada confi abilidade nos dois momentos de avaliação. No que tange à escala de funcionalidade, as funções física e cognitiva apresentaram melhora; e a função emocional, piora após três meses do tratamento. A escala de sintomas revelou piora, após três meses do início da quimioterapia, no que diz respeito aos sintomas de fadiga, náusea, dispneia, perda de apetite e diarreia. Conclusão: Neste estudo, os domínios mais afetados, após três meses de tratamento quimioterápico, estavam relacionados às funções da escala funcional e dos sintomas, portanto, intervenções multiprofi ssionais devem ser implementadas a esta população visando ao controle de tais variáveis.


Resumen Objetivo: Evaluar la calidad de vida relacionada con la salud (CVRS) de pacientes oncológicos antes del inicio del tratamiento de quimioterapia y tres meses después. Métodos: Se trató de un estudio de cohorte prospectivo, exploratorio. Fue utilizado un instrumento para la caracterización sociodemográfica y clínica de los pacientes y otro para la evaluación de la CVRS denominado EORTC QLQ-C30, que está compuesto por tres escalas: funcionalidad, síntomas y salud global. Participaron 70 individuos atendidos en consultorios externos para la realización de quimioterapia. Se realizaron pruebas estadísticas para comparar el efecto del tratamiento de quimioterapia con relación a la calidad de vida. Resultados: El instrumento EORTC QLQ-C30 indicó fiabilidad adecuada en los dos momentos de evaluación. En lo que atañe a la escala de funcionalidad, la función física y la cognitiva presentaron mejora, y la función emocional empeoró después de tres meses de tratamiento. La escala de síntomas reveló empeoramiento, luego de tres meses del inicio de la quimioterapia, en lo que se refiere a los síntomas de fatiga, náuseas, disnea, pérdida de apetito y diarrea. Conclusión: En este estudio, los dominios más afectados luego de tres meses de tratamiento de quimioterapia se relacionaron con funciones de la escala funcional y de los síntomas; por lo tanto, intervenciones multiprofesionales deben ser implementadas en esta población con el objetivo de controlar dichas variables.


Abstract Objective: To assess the health-related quality of life (HRQoL) of patients with cancer before and three months after starting chemotherapy treatment. Methods: This is a prospective and exploratory cohort study. An instrument was used for sociodemographic and clinical characterization of patients and another for assessing HRQoL called EORTC QLQ-C30. This instrument consists of functional, symptom, and global health status scales. Seventy-nine individuals attended at an outpatient clinic for chemotherapy. Statistical tests were performed to compare side effects of chemotherapy treatment on quality of life. Results: The EORTC QLQ-C30 indicated adequate reliability in two assessment moments. Concerning the functional scale, physical functioning and cognitive functioning improved, and emotional functioning worsened after three months of treatment. The symptom scale worsened three months after starting chemotherapy with respect to the symptoms of fatigue, nausea, dyspnea, appetite loss, and diarrhea. Conclusion: The most affected domains, after three months of chemotherapy treatment, were related to functional and symptom scales' functioning; therefore, multidisciplinary interventions should be implemented for this population in order to control such variables.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Quality of Life , Neoplasms/drug therapy , Neoplasms/epidemiology , Patient Care Team , Activities of Daily Living , Interviews as Topic , Prospective Studies , Cohort Studies , Evaluation Studies as Topic
12.
Microb Cell Fact ; 19(1): 90, 2020 Apr 15.
Article in English | MEDLINE | ID: mdl-32293464

ABSTRACT

BACKGROUND: Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren's (SDE) and 8 individuals with features of Sjögren's but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined. RESULTS: Results showed that Firmicutes was the dominant phylum in the gut, comprising 40-60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon's diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith's phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p = 0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs. CONCLUSIONS: In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.


Subject(s)
Actinobacteria/metabolism , Bacteroidetes/metabolism , Dysbiosis/metabolism , Gastrointestinal Microbiome , Sjogren's Syndrome/metabolism , Adult , Aged , Female , Humans , Male , Middle Aged
13.
Exp Eye Res ; 194: 108024, 2020 05.
Article in English | MEDLINE | ID: mdl-32246983

ABSTRACT

We report an analysis of the aqueous humor (AH) metabolome of primary open angle glaucoma (POAG) in comparison to normal controls. The AH samples were obtained from human donors [control (n = 35), POAG (n = 23)]. The AH samples were subjected to one-dimensional 1H nuclear magnetic resonance (NMR) analyses on a Bruker Avance 600 MHz instrument with a 1.7 mM NMR probe. The same samples were then subjected to isotopic ratio outlier analysis (IROA) using a Q Exactive orbitrap mass spectrometer after chromatography on an Accela 600 HPLC. Clusterfinder Build 3.1.10 was used for identification and quantification based on long-term metabolite matrix standards. In total, 278 metabolites were identified in control samples and 273 in POAG AH. The metabolites identified were fed into previously reported proteome and genome information and the OmicsNet interaction network generator to construct a protein-metabolite interactions network with an embedded protein-protein network. Significant differences in metabolite composition in POAG compared to controls were identified indicating potential protein/gene pathways associated with these metabolites. These results will expand our previous understanding of the impeded AH metabolite composition, provide new insight into the regulation of AH outflow, and likely aid in future AH and trabecular meshwork multi-omics network analyses.


Subject(s)
Aqueous Humor/metabolism , Eye Proteins/metabolism , Glaucoma, Open-Angle/metabolism , Intraocular Pressure/physiology , Trabecular Meshwork/metabolism , Aged , Aged, 80 and over , Case-Control Studies , Cell Differentiation , Female , Glaucoma, Open-Angle/pathology , Humans , Male , Mass Spectrometry , Middle Aged , Trabecular Meshwork/pathology
14.
Microb Cell Fact ; 19(1): 75, 2020 Mar 24.
Article in English | MEDLINE | ID: mdl-32204699

ABSTRACT

Resistance to therapy is one of the major factors that contribute to dismal survival statistics in pancreatic cancer. While there are many tumor intrinsic and tumor microenvironment driven factors that contribute to therapy resistance, whether pre-existing metabolic diseases like type 2 diabetes (T2D) contribute to this has remained understudied. It is well accepted that hyperglycemia associated with type 2 diabetes changes the gut microbiome. Further, hyperglycemia also enriches for a "stem-like" population within the tumor. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to gemcitabine/paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group. Additionally, we also observed an increase in the CD133+ tumor cells population in the T2D model. These observations indicated that in an animal model for T2D, microbial dysbiosis is associated with increased resistance to chemotherapeutic compounds.


Subject(s)
Diabetes Mellitus, Type 2/microbiology , Drug Resistance, Neoplasm , Dysbiosis/microbiology , Hyperglycemia/microbiology , Pancreatic Neoplasms/drug therapy , Animals , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Gastrointestinal Microbiome , Male , Mice , Mice, Inbred C57BL , Paclitaxel/therapeutic use , Pancreatic Neoplasms/microbiology , Gemcitabine , Pancreatic Neoplasms
15.
Carcinogenesis ; 41(5): 561-570, 2020 07 10.
Article in English | MEDLINE | ID: mdl-31369062

ABSTRACT

The lack of tools for early detection of pancreatic ductal adenocarcinoma (PDAC) is directly correlated with the abysmal survival rates in patients. In addition to several potential detection tools under active investigation, we tested the gut microbiome and its metabolic complement as one of the earliest detection tools that could be useful in patients at high risk for PDAC. We used a combination of 16s rRNA pyrosequencing and whole-genome sequencing of gut fecal microbiota in a genetically engineered PDAC murine model (KRASG12DTP53R172HPdxCre or KPC). Metabolic reconstruction of microbiome was done using the HUMAnN2 pipeline. Serum polyamine levels were measured from murine and patient samples using chromogenic assay. Our results showed a Proteobacterial and Firmicutes dominance in gut microbiota in early stages of PDAC development. Upon in silico reconstruction of active metabolic pathways within the altered microbial flora, polyamine and nucleotide biosynthetic pathways were significantly elevated. These metabolic products are known to be actively assimilated by the host and eventually utilized by rapidly dividing cells for proliferation validating their importance in the context of tumorigenesis. In KPC mice, as well as PDAC patients, we show significantly elevated serum polyamine concentrations. Therefore, at the early stages of tumorigenesis, there is a strong correlation between microbial changes and release of metabolites that foster host tumorigenesis, thereby fulfilling the 'vicious cycle hypothesis' of the role of microbiome in health and disease states. Our results provide a potential, precise, noninvasive tool for early detection of PDAC, which may result in improved outcomes.


Subject(s)
Carcinoma, Pancreatic Ductal/diagnosis , Dysbiosis/complications , Early Detection of Cancer , Gastrointestinal Microbiome , Pancreatic Neoplasms/diagnosis , Polyamines/metabolism , Animals , Carcinogenesis , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/microbiology , Carcinoma, Pancreatic Ductal/pathology , Dysbiosis/microbiology , Feces/microbiology , Female , Humans , Male , Mice , Mice, Transgenic , Mutation , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/microbiology , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Tumor Suppressor Protein p53/genetics
16.
Anal Chem ; 92(2): 2005-2010, 2020 01 21.
Article in English | MEDLINE | ID: mdl-31869197

ABSTRACT

Spatially targeted optical microproteomics (STOMP) is a method to study region-specific protein complexity in primary cells and tissue samples. STOMP uses a confocal microscope to visualize structures of interest and to tag the proteins within those structures by a photodriven cross-linking reaction so that they can be affinity purified and identified by mass spectrometry (eLife 2015, 4, e09579). However, the use of a custom photo-cross-linker and the requirement for extensive user intervention during sample tagging have posed barriers to the utilization of STOMP. To address these limitations, we built automated STOMP (autoSTOMP) which uses a customizable code in SikuliX to coordinate image capture and cross-linking functions in Zeiss Zen Black with image processing in FIJI. To increase protocol accessibility, we implemented a commercially available biotin-benzophenone photo-cross-linking and purification protocol. Here we demonstrate that autoSTOMP can efficiently label, purify, and identify proteins belonging to 1-2 µm structures in primary human foreskin fibroblasts or mouse bone marrow-derived dendritic cells infected with the protozoan parasite Toxoplasma gondii (Tg). AutoSTOMP can easily be adapted to address a range of research questions using Zeiss Zen Black microscopy systems and LC-MS protocols that are standard in many research cores.


Subject(s)
Automation , Proteins/analysis , Proteomics , Animals , Dendritic Cells/chemistry , Fibroblasts/chemistry , Humans , Mice , Molecular Structure , Optical Imaging , Protein Conformation
17.
Nursing (Ed. bras., Impr.) ; 23(263): 3698-3704, abr.2020.
Article in Portuguese | BDENF - Nursing, LILACS | ID: biblio-1100515

ABSTRACT

Objetivo: Caracterizar os processos éticos instaurados no Conselho Regional de Enfermagem de Mato Grosso do Sul, Brasil (COREN/MS). Método: trata-se de um estudo exploratório, descritivo e documental. As variáveis analisadas foram: denunciante, denunciado, desfecho do processo ético, artigos infringidos e penalidades aplicadas. A pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da Universidade Federal do Mato Grosso do Sul (parecer n.º 438.302). Resultados: Trinta e quatro processos éticos de 2003 a 2013 foram analisados. O COREN/MS foi o principal denunciante (47%), a maioria dos denunciados era auxiliar de enfermagem (44%). Houve aplicação de penalidades em 11 processos; os artigos infringidos apontaram que além de executarem práticas proibidas, houve descumprimento dos deveres e responsabilidades profissionais e, consequentemente, violação de princípios bioéticos. A penalidade mais aplicada foi advertência verbal (81%). Conclusão: O estudo das infrações éticas é fundamental para subsidiar a tomada de decisões referentes a políticas voltadas para melhorias tanto na formação como no exercício profissional da enfermagem. (AU)


Objective: To characterize the ethical processes established at the Regional Nursing Council of Mato Grosso do Sul, Brazil (COREN/MS). Method: this is an exploratory, descriptive and documentary study. The variables analyzed were whistleblower, denounced, outcome of the ethical process, violated articles and applied penalties. A research was approved by the Research Ethics Committee of the Federal University of Mato Grosso do Sul (opinion No. 438,302). Results: Thirty-four ethical processes were analyzed from 2003 to 2013. CORE /MS was the main whistleblower (47%), the majority of those reported in the nursing assistant era (44%). Penalties were applied in 11 cases; the violated articles pointed out that in addition to carrying out prohibited practices, there was a breach of professional duties and obligations and, consequently, violation of bioethical principles. The most applied penalty was announced verbally (81%). Conclusion: The study of ethical infractions is fundamental to support decision-making related to policies aimed at improving both training and professional nursing practice.(AU)


Objetivo: caracterizar los procesos éticos establecidos en el Consejo Regional de Enfermería de Mato Grosso do Sul, Brasil (COREN / MS). Método: se trata de un estudio exploratorio, descriptivo y documental. Las variables analizadas fueron: denunciante, denunciado, resultado del proceso ético, artículos violados y sanciones aplicadas. Una investigación fue aprobada por el Comité de Ética en Investigación de la Universidad Federal de Mato Grosso do Sul (opinión No. 438.302). Resultados: se analizaron Treinta y cuatro procesos éticos de 2003 a 2013. COREN/MS fue el principal denunciante (47%), la mayoría de los reportados en la era de los auxiliares de enfermería (44%). Se aplicaron sanciones en 11 casos; Los artículos violados señalaban que, además de llevar a cabo prácticas prohibidas, había una violación de los deberes y obligaciones profesionales y, en consecuencia, una violación de los principios bioéticos. La penalidad más aplicada se anunció verbalmente (81%). Conclusión: El estudio de las infracciones éticas es fundamental para apoyar la toma de decisiones relacionadas con políticas destinadas a mejorar tanto la capacitación como la práctica profesional de enfermería.(AU)


Subject(s)
Humans , Nurse's Role , Codes of Ethics , Ethics, Nursing , Ethics, Professional , Legislation, Nursing/ethics , Health Councils , Nurse Practitioners
18.
Rev. bras. enferm ; 72(5): 1279-1287, Sep.-Oct. 2019. tab
Article in English | LILACS, BDENF - Nursing | ID: biblio-1042138

ABSTRACT

ABSTRACT Objective: To analyze the knowledge about tuberculosis among nursing undergraduate students of a Federal Higher Education Institution. Method: Descriptive cross-sectional study, with quantitative approach. Data were collected through a questionnaire based on the WHO's guide to developing evaluation instruments on knowledge, attitudes and practices related to TB. Students were classified as "with knowledge" and "with little knowledge" based on the mean percentage of correct responses to the variables analyzed. Descriptive statistics techniques were used. Results: 60 nursing students were interviewed. "with little knowledge" was observed among students who were studying at the university for less time and who had no previous contact with the subject, and "with knowledge" was observed among those whose knowledge about tuberculosis was acquired in the health services. Conclusion: Knowledge gaps among undergraduate nursing students were identified, suggesting the need to rethink teaching-learning strategies on the subject.


RESUMEN Objetivo: analizar el conocimiento acerca de la tuberculosis entre alumnos de graduación de Enfermería de una Universidad Federal de Enseñanza Superior. Método: se trata de un estudio descriptivo, de abordaje cuantitativo, realizado de manera transversal. Los datos se recogieron con un cuestionario basado en la guía de la OMS para el desarrollo de instrumentos de evaluación sobre conocimientos, actitudes y prácticas relacionadas con la tuberculosis. Los alumnos se categorizaron en grupos de "conocimiento" y "poco conocimiento", según el promedio de respuestas para las variables analizadas. Se utilizaron técnicas de estadística descriptiva. Resultados: de los 60 alumnos entrevistados, se advirtió "poco conocimiento" entre los que tenían menos tiempo de estudio en la universidad y prácticamente ningún contacto anterior con el tema, y "conocimiento", entre aquellos que habían aprendido sobre la tuberculosis en los servicios de salud. Conclusión: el conocimiento sobre la tuberculosis entre alumnos de graduación de enfermería es exiguo, lo que demuestra la necesidad de repensar estrategias de enseñanza-aprendizaje sobre el tema.


RESUMO Objetivo: Analisar o conhecimento sobre a tuberculose entre alunos de graduação de Enfermagem de uma Universidade Federal de Ensino Superior. Método: Estudo descritivo realizado de maneira transversal, com abordagem quantitativa. Os dados foram coletados por meio de questionário elaborado com base no guia da OMS para desenvolvimento de instrumentos de avaliação de conhecimento, atitudes e práticas relacionados à tuberculose. Os alunos foram categorizados em grupos de "conhecimento" e "pouco conhecimento" com base no percentual médio de respostas para as variáveis analisadas. Utilizaram-se técnicas de estatística descritiva. Resultados: Entrevistaram-se 60 alunos de enfermagem. Observou-se "pouco conhecimento" entre alunos com menor tempo de estudo na universidade e sem contato prévio com o tema e "conhecimento" entre aqueles cujo conhecimento sobre a tuberculose foi adquirido nos serviços de saúde. Conclusão: Identificaram-se falhas no conhecimento entre alunos de graduação em enfermagem, sugerindo necessidade de repensar estratégias de ensino-aprendizagem sobre o tema.


Subject(s)
Humans , Male , Female , Adult , Students, Nursing/statistics & numerical data , Tuberculosis/nursing , Health Knowledge, Attitudes, Practice , Cross-Sectional Studies , Surveys and Questionnaires , Education, Nursing, Baccalaureate/methods , Education, Nursing, Baccalaureate/standards
19.
Rev Bras Enferm ; 72(5): 1279-1287, 2019 Sep 16.
Article in English, Portuguese | MEDLINE | ID: mdl-31531652

ABSTRACT

OBJECTIVE: To analyze the knowledge about tuberculosis among nursing undergraduate students of a Federal Higher Education Institution. METHOD: Descriptive cross-sectional study, with quantitative approach. Data were collected through a questionnaire based on the WHO's guide to developing evaluation instruments on knowledge, attitudes and practices related to TB. Students were classified as "with knowledge" and "with little knowledge" based on the mean percentage of correct responses to the variables analyzed. Descriptive statistics techniques were used. RESULTS: 60 nursing students were interviewed. "with little knowledge" was observed among students who were studying at the university for less time and who had no previous contact with the subject, and "with knowledge" was observed among those whose knowledge about tuberculosis was acquired in the health services. CONCLUSION: Knowledge gaps among undergraduate nursing students were identified, suggesting the need to rethink teaching-learning strategies on the subject.


Subject(s)
Health Knowledge, Attitudes, Practice , Students, Nursing/statistics & numerical data , Tuberculosis/nursing , Adult , Cross-Sectional Studies , Education, Nursing, Baccalaureate/methods , Education, Nursing, Baccalaureate/standards , Female , Humans , Male , Surveys and Questionnaires
20.
Methods Mol Biol ; 1996: 41-46, 2019.
Article in English | MEDLINE | ID: mdl-31127545

ABSTRACT

Various research strategies involving biomarker discovery and mechanistic studies in system biology depend on reproducible and reliable quantification of all metabolites from tissue(s) of interest. Contemporary analytical methods rely on mass spectrometry-based targeted and/or untargeted metabolomics platforms. The robustness of these analyses depends on the cleanliness of the samples, accuracy of the database, resolution of the instrument, and, the most variable of the list, the personal preferences of the researcher and the instrument operator. In this chapter, we introduce a simple method to prepare murine liver samples and carry it through the Isotope Ratio Outlier Analysis (IROA®) pipeline. This pipeline encompasses sample preparation, LC-MS-based peak acquisition, proprietary software-based library creation, normalization, and quantification of metabolites. IROA® offers a unique platform to create and normalize a local library and account for run-to-run variability over years of acquisition using the internal standards (IROA®-IS) and long-term reference standards (IROA®-LTRS).


Subject(s)
Metabolomics/methods , Radioisotopes/analysis , Animals , Chromatography, High Pressure Liquid/methods , Chromatography, High Pressure Liquid/standards , Liver/metabolism , Mass Spectrometry/methods , Mass Spectrometry/standards , Metabolomics/standards , Mice , Reference Standards , Reproducibility of Results , Software
SELECTION OF CITATIONS
SEARCH DETAIL
...